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The role of alisertib in treatment of peripheral T-cell lymphomas
1Department of Clinical Oncology, Velindre Cancer Centre, Cardiff, CF14 2TL, Wales, UK.
Abstract:
Peripheral T-cell lymphomas are aggressive lymphomas with poor outcomes for which novel treatments are urgently needed. Alisertib (MLN8237) is a second-generation oral Aurora A kinase inhibitor. Treatment with alisertib results in an accumulation of cells with abnormal mitotic spindles, leading to decreased proliferation and apoptosis in a range of human tumor cell lines. Alisertib has shown single-agent antitumor activity in animal xenograft models and promising antitumor activity alone or in combination with other agents in patients with solid and hematologic cancers, and T-cell lymphomas in particular. It is currently being tested in randomized controlled Phase III trials in relapsed/refractory peripheral T-cell lymphoma.
Insights
Alisertib, an Aurora A kinase inhibitor, shows promise in treating aggressive peripheral T-cell lymphomas. This novel drug is currently in Phase III trials for relapsed or refractory cases.
Area of Science:
- Oncology
- Pharmacology
Background:
- Peripheral T-cell lymphomas (PTCLs) are aggressive cancers with limited treatment options and poor prognoses.
- Novel therapeutic strategies are essential for improving outcomes in PTCL patients.
Purpose of the Study:
- To evaluate the efficacy of alisertib, an Aurora A kinase inhibitor, as a potential treatment for peripheral T-cell lymphomas.
Main Methods:
- Alisertib targets Aurora A kinase, leading to mitotic spindle abnormalities, reduced cell proliferation, and apoptosis in various cancer cell lines.
- Antitumor activity of alisertib was assessed in preclinical xenograft models and early-phase clinical trials for solid and hematologic malignancies, including T-cell lymphomas.
Main Results:
- Alisertib demonstrated single-agent antitumor activity in animal models.
- Promising antitumor effects were observed in patients with various cancers, particularly T-cell lymphomas, both as a monotherapy and in combination regimens.
Conclusions:
- Alisertib exhibits significant antitumor potential in preclinical and early clinical studies for T-cell lymphomas.
- Ongoing Phase III clinical trials are investigating alisertib in relapsed/refractory PTCL, representing a critical step in its development.
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